MON-268 A Rare Case of Primary Hypoaldosteronism in a Newborn

BACKGROUND: Primary aldosterone synthase deficiency (ASD) is a rare but potentially life-threatening cause of mineralocorticoid deficiency primarily due to a defect in CYP11B2, which encodes aldosterone synthase. There are two types of ASDs, both resulting in primary hypoaldosteronism, but due to differences in blockade of the terminal oxidation step, are distinguished by low 18-hydroxycorticosterone (18-OHC) in Type 1 and elevated 18-OHC in Type 2. With a wide variation in clinical severity and presentation, few cases of ASD have been reported. CLINICAL CASE: A 10-day old full term male infant born to unrelated parents of European descent presented with weight loss, poor feeding and dehydration, in the setting of hyponatremia (Na 127 mM, ref 131-145 mM) and hyperkalemia (K 8 mM, ref 3.2-6 mM). He had normal genitalia and no hyperpigmentation on exam. A cosyntropin stimulation test resulted in a cortisol of 19 μg/dL. Electrolytes transiently improved with normal saline but worsened after fluids were discontinued. Oral NaCl was initiated at a dose of 4 mEq/kg/day and titrated to 6 mEq/kg/day. Aldosterone levels while hyponatremic were inappropriately low (<35 ng/dL, ref <218 ng/dL) with elevated plasma renin activity (PRA) of 112 ng/mL/hr (ref 0.25-5.82 ng/mL/hr), consistent with primary hypoaldosteronism. On day 14 of life, fludrocortisone was started at 0.05 mg/day and increased to 0.2 mg/day until Na and K levels normalized. At 20 days of life he was discharged, only to return 3 days later with isolated hyperkalemia (K 6.4 mM), PRA elevation to 80 ng/mL/hr, and lethargy. Prior 18-OHC and corticosterone levels returned significantly low at <26 ng/dL and <40 ng/dL respectively, consistent with a diagnosis of Type 1 ASD. Subsequently, fludrocortisone was increased to 0.3 mg/day and NaCl to 8 mEq/kg/day. At 6 months, the infant continues to do well though growth velocity remains slightly impacted. However, due to suppressed PRA levels and hypertension on exam, fludrocortisone was reduced to 0.05 mg/day and NaCl to 4.5 mEq/kg/day. Given the rarity of Type 1 ASD, he was referred for genetic counseling to obtain molecular confirmation. CONCLUSION: This is a rare case of Type 1 ASD diagnosed in early infancy based on inappropriately low 18-OHC and aldosterone levels during times of hyponatremia or hyperkalemia requiring high doses of mineralocorticoid and salt replacement in the first few months of life. While ASD is generally considered less severe than CAH, it can present with recurrent dehydration, salt wasting and failure to thrive, and be lethal if not recognized promptly. Despite timely treatment, growth retardation can still occur. Long term follow-up is needed to better understand the natural history of ASD, though clinical severity may decrease with age. As it is not included in newborn screening, this case highlights the importance of suspecting ASD in infants with hyponatremia and hyperkalemia.